Kies M S, Haraf D J, Athanasiadis I, Kozloff M, Mittal B, Pelzer H, Rademaker A W, Wenig B, Weichselbaum R R, Vokes E E
Department of Medicine, Northwestern University Medical School and the Lurie Cancer Center, Chicago, IL, USA.
J Clin Oncol. 1998 Aug;16(8):2715-21. doi: 10.1200/JCO.1998.16.8.2715.
To determine tumor response rate, patterns of failure, toxicity, and survival in advanced squamous head and neck cancer after a combined treatment program that consists of induction chemotherapy, organ-sparing surgery, and concurrent chemoradiation. Long-term outcome data are presented.
Between July 1991 and March 1993, 93 patients received three cycles of induction chemotherapy that consisted of cisplatin, fluorouracil (5-FU), l-leucovorin, and alpha-interferon2b (PFLl-alpha) followed by optional limited surgery and six to eight cycles of 5-FU, hydroxyurea, and concurrent radiation (FHX) to a total radiation dose of 65 to 75 Gy.
Ninety-three patients were entered onto this study and 97% had stage IV disease, with 66 patients who were N2 or N3. Sixty-one patients (66%) achieved a clinical complete remission (CR) after induction therapy. Thirty-four patients underwent surgery. Seventy-nine patients proceeded to FHX. With a median follow-up time of 43 months for surviving patients, 20 patients have had disease progression (13 local, two distant, five both), and there have been 35 deaths (18 from disease, six treatment-related, two from a second primary, and nine for other medical reasons). At 5 years, progression-free survival is 68%, and overall survival is 62%. Surgery was organ-preserving, as only a single laryngectomy and no glossectomies were performed in primary management. Acute toxicity related to PFLl-alpha consisted of severe or life-threatening mucositis in 57% and leucopenia in 65% of patients. During FHX, 81% of patients had grade 3 or 4 mucositis.
PFLl-alpha is a highly active regimen that induced clinical CR in two thirds of patients. When followed by limited surgery and FHX, resultant local and distant disease control, organ preservation, and overall 5-year survival are very promising in high-risk stage IV patients. Based on these local control and survival data, further evaluation of this treatment sequence, induction chemotherapy followed by concurrent chemoradiation, is warranted. Identification of similarly active but less toxic regimens is a high priority.
确定在由诱导化疗、保留器官手术和同步放化疗组成的联合治疗方案后，晚期头颈部鳞状细胞癌的肿瘤缓解率、失败模式、毒性和生存率。呈现长期结局数据。
1991年7月至1993年3月期间，93例患者接受了三个周期的诱导化疗，化疗方案为顺铂、氟尿嘧啶（5-FU）、亚叶酸钙和α-干扰素2b（PFL1-α），随后进行选择性有限手术，以及六至八个周期的5-FU、羟基脲和同步放疗（FHX），总放疗剂量为65至75 Gy。
93例患者进入本研究，97%为IV期疾病，66例为N2或N3期。61例患者（66%）在诱导治疗后达到临床完全缓解（CR）。34例患者接受了手术。79例患者进行了FHX。存活患者的中位随访时间为43个月，20例患者出现疾病进展（13例为局部进展，2例为远处进展，5例为局部和远处均进展），35例患者死亡（18例死于疾病，6例与治疗相关，2例死于第二原发肿瘤，9例死于其他医学原因）。5年时，无进展生存率为68%，总生存率为62%。手术保留了器官，因为在初始治疗中仅进行了1例喉切除术，未进行舌切除术。与PFL1-α相关的急性毒性包括57%的患者出现严重或危及生命的粘膜炎，65%的患者出现白细胞减少。在FHX期间，81%的患者出现3级或4级粘膜炎。
PFL1-α是一种高度有效的方案，可使三分之二的患者达到临床CR。在随后进行有限手术和FHX后，对于高危IV期患者，由此产生的局部和远处疾病控制、器官保留以及5年总生存率非常有前景。基于这些局部控制和生存数据，有必要进一步评估这种治疗顺序，即诱导化疗后进行同步放化疗。确定同样有效但毒性较小的方案是当务之急。
